Induction of apoptosis by hydroxydibenzoylmethane through coordinative modulation of cyclin D3, Bcl-X(L), and Bax, release of cytochrome c, and sequential activation of caspases in human colorectal carcinoma cells.

Abstract

DBM (dibenzoylmethane) is a minor constituent of licorice that has antimutagenic activity. However, its other biological activities are not well-known. The structurally related beta-diketones hydroxydibenzoylmethane (HDB) and hydroxymethyldibenzoylmethane (HMDB) were able to induce apoptosis in colorectal carcinoma COLO 205 cells. Thus, the effect of structurally related beta-diketones on cell viability, DNA fragmentation, and caspase activity was assessed. The potency of these compounds on these features of apoptosis were in the order of HDB > HMDB > DBM in colorectal carcinoma COLO 205 cells. Here, we found that HDB-induced apoptotic cell death was accompanied by upregulation of cyclin D3, Bax, and p21 and down-regulation of Bcl-X(L), while HDB had no effect on the levels of Bcl-2 and Bad protein. These results indicate that HDB allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 degradation. It is suggested that HDB-induced apoptosis is triggered by the release of cytochrome c into cytosol, procaspase-9 processing, activation of caspase-3 and caspase-2, degradation of PARP, and DNA fragmentation caused by the caspase-activated deoxyribonuclease through the digestion of DFF-45. The induction of apoptosis by HDB may provide a pivotal mechanism for its cancer chemopreventive action.

• Authors: Min-Hsiung Pan, Mei-Chen Huang, Ying-Jan Wang, Jen-Kun Lin, Chao-Hsien Lin
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 51 Issue 14 Pg. 3977-84 (Jul 02 2003) ISSN: 0021-8561 [Print] United States
• PMID: 12822933 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• BAX protein, human
• BCL2L1 protein, human
• Benzoates
• CCND3 protein, human
• Caspase Inhibitors
• Chalcones
• Cyclin D3
• Cyclins
• Cytochrome c Group
• Enzyme Inhibitors
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• bcl-X Protein
• hydroxydibenzoylmethane
• dibenzoylmethane
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Benzoates (pharmacology)
• Caspase 3
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Survival (drug effects)
• Chalcones
• Colorectal Neoplasms (metabolism, pathology)
• Cyclin D3
• Cyclins (genetics)
• Cytochrome c Group (metabolism)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Gene Expression (drug effects)
• Humans
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Tumor Cells, Cultured
• bcl-2-Associated X Protein
• bcl-X Protein